We aim to study the mechanisms of, and compensations for, restrictions to flow through the pulmonary circulation. The previous program focused on mechanical factors affecting edema and the pulmonary circulation and the treatment of the edema of ARDS. Through a series of studies showing the importance to fluid fluxes and vascular volumes of interstitial pressures in the lungs, a diagnostic test for edema based on lung density (Compton scatter) evolved. Although treatment of ARDS edema by PEEP was shown to have no effect on the healing of the oleic acid ARDS lesion the PEEP studies led to a clarification of the effects of lung volume and pressure on the pulmonary circulation, cardiac output and cerebral blood flow. Building on this, the first focus of the present program is on causes of pulmonary blood flow restriction. There is a further study of mechanisms of edema formation (1 project), but the emphasis is on hypoxic pulmonary vasoconstriction and thrombotic obstruction (2 projects). The second focus is the compensation for pulmonary blood flow restriction (which, as when due to hypoxic vasoconstriction, may itself be a response to a primary lung lesion), particularly the role of the bronchial circulation, and the systemic response to a raised right heart pressure (3 projects). These 6 projects are supported by Aministrative, Arachidonic Acid Metabolite, and Morphology cores. The approach is multidisciplinary, with investigators trained in medicine, physiology, anesthesiology, pediatrics, pathology and biochemistry. It is a result of more than a decade of interest in the pulmonary circulation and lung edema by the investigators, among whom there is a long history of collaboration. The program is designed to support other clinical research in ARDS, pulmonary vascular disease, and lung edema which is proceeding at this institution. The strengths of the proposal include the integration of many disciplines, the experience with unique techniques for investigating the pulmonary and bronchial circulations, and the productivity of this group of investigators.